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Faced with growing drug expenditures, drug insurance plan executives have adopted various cost containment measures. One such policy, reference pricing (RP), limits drug plan reimbursement of interchangeable medicines to a reference price, which is typically equal to the price of the lowest cost interchangeable drug; any cost above that is borne by the patient. RP policies vary in the extent to which drugs are considered interchangeable by a particular plan (Lopez-Casasnovas and Puig-Junoy 2000). Under its most restrictive form—Type 1 RP—only chemically equivalent drugs (i.e., branded and “generic” versions of the same drug) are considered interchangeable. Under Type 2 RP, all drugs from the same therapeutic class are considered interchangeable. For instance, under such a system all nonsteroidal antiinflammatory drugs (NSAIDs), used for analgesia, would be reimbursed at the same rate. Under Type 3 RP, by contrast, all the different analgesic drugs, including opiates and NSAIDs, would be considered interchangeable. There have been calls to integrate RP into the Medicare prescription drug benefit (Huskamp et al. 2000; Morgan, Barer, and Agnew 2003). Unlike traditional patient cost sharing policies, RP fully subsidizes lower cost medicines, and, for those who meet exemption criteria, higher cost medicines as well. RP might therefore save money while avoiding the adverse impacts on patient health associated with patient cost sharing, which typically applies to all drugs (Tamblyn et al. 2001). While the debate on whether RP should be widely used in the U.S. has been heated, evidence on its outcomes is limited (Kanavos and Reinhardt 2003). In this paper, we use retrospective population-based claims data to compare the net drug program savings realized by the application of Type 1 and then Type 2 RP with the NSAIDs by Pharmacare, the publicly funded drug subsidy program for seniors and various other residents of British Columbia (BC), Canada. NSAIDs are among the most commonly used medications worldwide, with over 70 million prescriptions and more than 30 billion over-the-counter tablets sold each year in the U.S. (Wolfe, Lichtenstein, and Singh 1999). Over 15 percent of North Americans suffer from arthritis and/or musculoskeletal disease (Lawrence et al. 1998), and current guidelines endorse both NSAIDs and acetaminophen as first-line therapies for symptomatic osteoarthritis (ACR 2000). Potential program savings from RP depend on the vector of reimbursement prices of the drugs considered interchangeable as well as on the quantities dispensed. Potential savings are greatest when use is skewed toward higher priced drugs and the price spread—the difference between the highest and lowest drug prices—is large. The price spread can only increase (or at least not decrease) the greater the number of drugs that are deemed interchangeable; potential savings are therefore largest for Type 3 RP and lowest for Type 1 RP. There were considerable differences in the prices of the different NSAIDs in BC prior to the introduction of Type 2 RP. The cost of generic ibuprofen, for instance, varied between $0.11 and $0.16 per day (depending on the amount used), whereas the daily cost of a newer NSAID, etodolac, varied from $1.79 to $3.58 (Therapeutics Initiative 1995). Several factors can mitigate drug plan savings from RP. The first of these is the generosity of the criteria, if any, by which patients are exempted from RP. Pharmacare exempts patients who have failed or are likely to fail on a lower cost, fully reimbursed drug. Although the physician must submit a written petition for review by Pharmacare's pharmacist personnel, exemption requests are usually granted within 48 hours. Pharmacare also exempts all NSAID prescriptions written by rheumatologists from Type 2 RP. Second, physicians might “prescribe around” the RP restrictions. In other words, they might substitute relatively costly analgesic drugs, including various opiates, that are not subject to RP for those that are. Third, economic theory suggests that setting reimbursement rates according to the prices of a set of reference standard drugs might encourage the manufacturers of those drugs to raise retail prices (Zweifel and Crivelli 1996; Morton 1997; Anis and Wen 1998). On the other hand, experience from Type 2 RP introduced in European countries suggests that such price increases are offset by decreases in the retail prices of drugs that are only partially reimbursed by drug plans. Fourth, although the drug plan saves money on those beneficiaries who elect to pay extra for the higher cost drugs, these expenditures are merely shifted—overall drug costs do not decline. Finally, the health of patients who switch to lower quality drugs might suffer, resulting in an off-setting increase in drug and other treatment costs. While we do not have data on patient health outcomes and individual patients commonly report better efficacy and/or tolerability with particular NSAIDs (Walker, Chan, and Yood 1992; Langman et al. 2001), we note that there is no consistent evidence of clinically significant differences in the anti-inflammatory and analgesic effect of the numerous different NSAIDs (Brooks and Day 1991; Holbrook 2001). Retrospective analyses of observational data have suggested a hierarchy among conventional NSAIDs in their potential for gastrointestinal injury, but these differences can be attributed to variations in effective dose and channeling bias (Henry et al. 1996; Rodriguez 1998). Others have studied the effects of prior authorization programs targeting higher cost NSAIDs on the health-related quality of life (Momani, Madhavan, and Nau 2002) and medical services use (Kotzan et al. 1993; Smalley et al. 1995) of chronic NSAID users enrolled in various U.S. state Medicaid programs. None of these studies detected any deleterious effects among those who were denied Medicaid subsidies for the higher cost NSAIDs. To address the net effect of Type 1 and 2 RP on Pharmacare and patient analgesic expenditures, we used monthly Pharmacare claims data aggregated across its senior (age 65+ years) beneficiaries, over the period February 1993 to June 2001, to examine prescribing patterns, NSAID prices, Pharmacare expenditure, and patient out-of-pocket expenditure on individual NSAIDs and other analgesic drugs. A previous report indicated high accuracy and completeness of provincial government drug claims data (Williams and Young 1996a Williams and Young 1996b). We focused on seniors given that they are the highest per capita users of analgesics (Health Canada 2003), and the size and composition of the beneficiary population is relatively stable over time.

Abstract Objectives To assess the added value of gadoxetic-acid–enhanced T1-weighted magnetic resonance Cholangiography (T1W-MRC) including controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA)-Volumetric Interpolated Breathhold (VIBE) technique compared to T2-weighted MR Cholangiography (T2W-MRC) in depicting biliary anatomy in potential living liver donors. Methods Eighty-five potential donors including 34 men with a mean age of 35.6 years (range, 18–55 years) and 51 women with a mean age of 36.7 years (range, 23–57 years), were enrolled in this ethics-approved retrospective study. Image quality for depiction of bile ducts was evaluated by two readers in consensus in 3 separate reading sessions: 1) T2W-MRC alone, 2) T1W-MRC alone (including CAIPI-VIBE and generalized autocalibrating partially parallel acquisitions (GRAPPA)-VIBE techniques, and 3) combined T1W/T2W-MRC. Accuracy of T2W-MRC, T1W-MRC, and combined T1W/T2W-MRC for the identification/classification of the biliary variants was calculated using intraoperative cholangiogram (IOC) as the reference standard. Image quality and reader diagnostic confidence provided by CAIPI-VIBE technique was compared with GRAPPA-VIBE technique. Datasets were compared using the Wilcoxon signed-rank test. Results Image quality for depiction of the bile ducts was significantly superior in the combined T1W/T2W-MRC group, when compared to each of T2W-MRC and T1W-MRC groups independently (P value = 0.001–0.034). The combination of CAIPI-VIBE and GRAPPA-VIBE was superior compared to each of the sequences individually. The accuracy of T2W-MRC and T1W-MRC was 93% and 91%, respectively. T1W-MRC depicted four biliary variants better than T2W-MRC. Two variants not well seen in T2W-MRC were clearly shown on T1W-MRC. Conclusion Gadoxetic-acid–enhanced T1W-MRC and conventional T2W-MRC techniques are complementary for depiction of biliary variants in potential liver donors and the combination of the two improves the results. The combination of CAIPI-VIBE and GRAPPA-VIBE techniques appear to be complementary for optimal diagnostic yield of T1W-MRC.

Upon ingestion, probiotics may act to protect the host through a number of protective mechanisms including modulation of genes involved in intestinal innate mucosal defense such as epithelial cell-derived mucin glycoproteins and inhibitor of apoptosis proteins. To determine the specificity of effect and sustainability of response in vivo, Lactobacillus plantarum 299v (Lp299v), Lactobacillus rhamnosus R0011 (LrR0011), and Bifidobacterium bifidum R0071 (BbR0071) were added repeatedly or intermittently to the drinking water of Sprague-Dawley rats. After killing the rats via CO2 suffocation, Muc2, Muc3, neuronal apoptosis inhibitor protein (NAIP), human inhibitor of apoptosis protein 1/cellular inhibitor of apoptosis 2 (HIAP1/cIAP2), and human inhibitor of apoptosis protein 2/cellular inhibitor of apoptosis 1 (HIAP2/cIAP1) mRNA and protein levels were analyzed via RT-PCR and immunohistochemistry. Live Lp299v, BbR0071, and LrR0011 increased Muc3 protein and mRNA expression in jejunum and ileum. Heat-killed and a nonadherent derivative of Lp299v failed to induce Muc3 expression. Lp299v did induce expression of HIAP2/cIAP1 and NAIP expression. Muc3 mucin expression was elevated for 5 d after oral administration of Lp299v; however, this effect was not sustained despite ongoing daily ingestion of a probiotic. Intermittent pulse ingestion of probiotics, however, was found to repeatedly increase Muc3 expression. We conclude that selected probiotics can induce protective genes of mucosal intestinal epithelial cells, an effect that is reproducible with pulse probiotic administration.

The clinical findings of patients with oral Kaposi's sarcoma are reviewed. These oral findings commonly included candidiasis, hairy leukoplakia, gingivitis associated with human immunodeficiency virus (HIV), periodontitis, and other symptoms, including xerostomia. The other common symptoms of HIV disease that may be of importance in leading to a diagnosis are reviewed in this patient group. Treatment by local radiotherapy or by intralesional vinblastine of these oral Kaposi's sarcomas resulted in successful palliation, with more than 50% regression of the lesions in 80% of the patients treated.

Cet article analyse l’évolution de la participation des femmes aux structures dirigeantes des associations. Les femmes apparaissent largement en retrait des fonctions de président d’association et leur accession aux postes de dirigeants s’effectue principalement à partir des associations créées récemment et dans des types d’associations orientées vers des populations fragiles ou vulnérables. L’article montre que l’on peut imputer leur plus forte présence essentiellement aux évolutions sociétales en cours depuis les années 70 : activité croissante des femmes, hausse de leur qualification, démocratisation de la société et de la vie associative, ouverture plus grande des associations récentes aux plus jeunes et à des catégories sociales plus variées. This article examines the evolution of the participation of women in the governing bodies of nonprofit organizations. There appear to be very few women CEOs in nonprofit organizations, and women who have reached executive positions have mainly done so in recently created nonprofit organizations and those concerned with people at risk and vulnerable social groups. The article shows that the increase is essentially due to societal changes since the 1970s: growing female participation in the workforce, their higher level of education, democratization of society and nonprofit organizations, and recent nonprofit organizations more open to younger people and a broader cross-section of the population.

Let k be a base field, K be a field containing k and L/K be a field extension of degree n. The essential dimension ed(L/K) over k is a numerical invariant measuring "the complexity" of L/K. Of particular interest is $\tau$(n) = max { ed(L/K) | L/K is a separable extension of degree n}, also known as the essential dimension of the symmetric group $S_n$. The exact value of $\tau$(n) is known only for n $\leq$ 7. In this paper we assume that k is a field of characteristic p > 0 and study the essential dimension of inseparable extensions L/K. Here the degree n = [L:K] is replaced by a pair (n, e) which accounts for the size of the separable and the purely inseparable parts of L/K respectively, and \tau(n) is replaced by $\tau$(n, e) = max { ed(L/K) | L/K is a field extension of type (n, e)}. The symmetric group $S_n$ is replaced by a certain group scheme $G_{n,e}$ over k. This group is neither finite nor smooth; nevertheless, computing its essential dimension turns out to be easier than computing the essential dimension of $S_n$. Our main result is a simple formula for \tau(n, e). Comment: 18 pages

EBEX is a NASA-funded balloon-borne experiment designed to measure the polarization of the cosmic microwave background (CMB). Observations will be made using 1432 transition edge sensor (TES) bolometric detectors read out with frequency multiplexed SQuIDs. EBEX will observe in three frequency bands centered at 150, 250, and 410 GHz, with 768, 384, and 280 detectors in each band, respectively. This broad frequency coverage is designed to provide valuable information about polarized foreground signals from dust. The polarized sky signals will be modulated with an achromatic half wave plate (AHWP) rotating on a superconducting magnetic bearing (SMB) and analyzed with a fixed wire grid polarizer. EBEX will observe a patch covering ~1% of the sky with 8' resolution, allowing for observation of the angular power spectrum from \ell = 20 to 1000. This will allow EBEX to search for both the primordial B-mode signal predicted by inflation and the anticipated lensing B-mode signal. Calculations to predict EBEX constraints on r using expected noise levels show that, for a likelihood centered around zero and with negligible foregrounds, 99% of the area falls below r = 0.035. This value increases by a factor of 1.6 after a process of foreground subtraction. This estimate does not include systematic uncertainties. An engineering flight was launched in June, 2009, from Ft. Sumner, NM, and the long duration science flight in Antarctica is planned for 2011. These proceedings describe the EBEX instrument and the North American engineering flight. 12 pages, 9 figures, Conference proceedings for SPIE Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy V (2010)

Children learn information from a variety of sources and often remember the content but forget the source. Whereas the majority of research has focused on retrieval mechanisms for such difficulties, the present investigation examines whether the way in which sources are encoded influences future source monitoring. In Study 1, 86 children aged 3 to 8 years participated in 2 photography sessions on different days. Children were randomly assigned to either the Difference condition (they were asked to pay attention to differences between the 2 events), the Memory control condition (asked to pay attention with no reference to differences), or the No-Instruction control (no special instructions were given). One week later, during a structured interview about the photography session, the 3- to 4-year-olds in the No-Instruction condition were less accurate and responded more often with 'do not know' than the 7- to 8-year-olds. However, the older children in the Difference condition made more source confusions than the younger children suggesting improved memory for content but not source. In Study 2, the Difference condition was replaced by a Difference-Tag condition where details were pointed out along with their source (i.e., tagging source to content). Ninety-four children aged 3 to 8 years participated. Children in the Difference-Tag condition made fewer source-monitoring errors than children in the Control condition. The results of these 2 studies together suggest that binding processes at encoding can lead to better source discrimination of experienced events at retrieval and may underlie the rapid development of source monitoring in this age range. (PsycINFO Database Record

Stent-based drug delivery system is a revolutionary approach to mitigate the negative affects of balloon angioplasty, improve immune responsiveness and prevent hyperplastic growth of smooth muscle in the restenotic state. Its success is therefore empirically associated with effective delivery of potent therapeutics to the target site at a therapeutic concentration, for a sufficient time, and in a biologically active form. However, local delivery with drug-eluting stents imparts large dynamic concentration gradients across tissues that can be difficult to identify, characterize and control. This review explores the factors such as physiological transport forces, drug physicochemical properties, local biological tissue properties and stent design that governs the local pharmacokinetics within the arterial wall by drug-eluting stent. Rational design and optimization of drug-eluting stents for local delivery thus requires a careful consideration of all these factors.